1. Field of the Invention
This invention relates to the determination of the specific gravity or osmolality of a liquid. More specifically, the present invention lends itself to accurate determinations of the specific gravity or osmolality of a liquid when nonionized solutes, such as urea and glucose, are present in the sample.
2. Description of the Prior Art
There are numerous arts in which it is useful to know the osmolality or specific gravity of a liquid. Such arts include brewing, urinalysis, water purification, etc. Needless to say, a quick, facile method for determining these parameters would greatly advance the state of many scientific disciplines, as well as any technology where rapid, accurate determination of these liquid characteristics would be beneficial. Thus, for example, if a medical laboratory technician could accurately measure these properties in urine samples in a matter of seconds, not only would a patient be afforded rapid results to aid the physician in diagnosis, but also laboratory efficiency would increase to a degree where many more analyses could be performed than were heretofore possible.
Although the present invention lends itself to a vast range of applications, for purposes of clarity this discussion will be couched largely in terms of the determination of osmolality or specific gravity of urine. Applications to other disciplines will become apparent from an understanding of how this invention relates to urinalysis.
The determination of urine osmolality is of considerable value in the understanding and clinical management of water electrolyte disturbances. Hence, complete urinalysis should, and usually does, include an osmolality determination.
Osmolality is a colligative property of a given solution, and is therefore related to freezing point, melting point, boiling point, vapor pressure, and osmotic pressure -- also colligative properties. It is a function of the number of particles in solution, as opposed to their weight or density.
Osmolality is mathematically defined by the following relationship EQU Osm = .phi.nm
where Osm is the osmolality of a solution, .phi. is the dissociation constant of the solutes, n is the number of dissociated ions per molecule of dissociated solute, and m is the molality of the solution. Hence, as the solutes approach complete dissociation, .phi. approaches unity and the equation reduces to EQU Osm = nm,
the equation for an ideal electrolyte.
Whereas a close correlation exists between osmolality and specific gravity in a solution containing a single solute, the correlation markedly diminishes in complex solutions containing nonionic species. Urine is a prime example of such a solution which deviates from ideal electrolytes. For example in one study urine specific gravities of 1.016 correspond to osmolalities ranging from 550 to 910 m Osm/kg. (T. Rodman, et al.; Journal of the American Medical Association: 167: 172, 1958).
Prior art methods for determining osmolality include the use of various commercially available osmometers which vary from manual to fully automated operation. For clinical work, however, freezing point measurement is usually chosen because of its relative simplicity. However, such procedures are fraught with many disadvantages. They are time-consuming, requiring steps of centrifugation to remove solids, super cooling below the freezing point, crystallization, and waiting for the temperature to rise to the actual freezing point.
Prior art methods for determining specific gravity utilize hydrometers, urinometers, pycnometers, gravimeters, and the like. Although these prior art procedures are satisfactorily sensitive, they all require fragile, bulky instruments which must be constantly cleaned, maintained, and calibrated to continuously assure their reliability. In addition, there are many inconveniences associated with the mechanics of using these instruments. There may be difficulty in reading the meniscus. Froth or bubbles on the liquid surface may interfere with the reading. There is a tendency for urinometers to adhere to the sides of the vessel containing the liquid sample. In the case of urine, the sample is frequently inadequate for floating a urinometer.
A recent breakthrough in which all of the above disadvantages have been virtually eliminated, and which affords extremely rapid osmolality determination, is disclosed in U.S. Ser. No. 647,416, filed by Greyson, et al. on Jan. 8, 1976 and assigned to the assignee of this application. Application Ser. No. 647,416 describes an invention in which a carrier matrix is incorporated with osmotically fragile microcapsules, the walls of which are composed of a semipermeable polymeric membrane material. Encapsulated inside the walls is a solution containing a coloring substance. When the capsules are in contact with a solution having a different osmolality than that within the capsules, an osmotic gradient is created across the capsule walls. This gradient causes solvent to permeate the capsule walls in the direction of the higher osmolality. Hence, if the internal liquid contains a higher number of particles per unit volume than the sample, solvent will flow into the capsules, tending to dilute their contents. Because of this phenomenon, the hydrostatic pressure within the capsules increases, causing swelling and/or rupture and the concomitant release of coloring substance. The rate and extent of release of the microcapsule contents is a function of the initial osmotic gradient across the capsule wall, and, hence, of the osmolality or specific gravity of the liquid external to the capsule. This technique is thoroughly described and taught in the above-cited patent application, which is hereby incorporated into the present disclosure by reference.
The microcapsule technique enables the laboratory technician to simply dip one carrier matrix into a urine sample, remove it, and observe any change in color. Hence, it can be seen that microcapsules represent a marked improvement over the art.
However, as stated supra, urine is a complex solution, containing nonionized solutes such as urea and glucose. When urine is contacted by the microcapsules, these molecules can permeate the microcapsule walls along with the solvent, thereby creating an inherent inaccuracy. It is to this problem of inaccuracy that the research leading up to the present invention was directed. The fruits of that research provide a technique for measuring osmolality or specific gravity of a liquid containing nonionic solutes with a dramatically enhanced degree of accuracy.